This study investigated the association between COVID-19 severity, gut microbiota dysbiosis, altered tryptophan metabolism, and dysregulated inflammatory responses. Analysis of metagenomic, metabolomic, cytokine, and transcriptomic profiles from hospitalized COVID-19 patients and controls revealed that severe COVID-19 was linked to depleted beneficial gut microbes and altered tryptophan metabolite levels. Reduced tryptophan metabolites correlated with decreased *Faecalibacterium* abundance and increased inflammatory cytokine production. These findings suggest a potential link between microbiome and metabolome alterations and inflammatory dysregulation in severe COVID-19.

Morgan Essex, Belén Millet Pascual-Leone, Ulrike Löber, Matthias Kuhring, Bowen Zhang, Ulrike Brüning, Raphaela Fritsche-Guenther, Marta Krzanowski, Facundo Fiocca Verneño, Sophia Brumhard, Ivo Röwekamp, Agata Anna Bielecka, Till Robin Lesker, Emanuel Wyler, Markus Landthaler, Andrej Mantei, Christian Meisel, Sandra Caesar, Charlotte Thibault, Victor M. Corman, Lajos Marko, Norbert Suttorp, Till Strowig, Florian Kurth, Leif E. Sander, Yang Li, Jennifer A. Kirwan, Sofia K. Forslund, Bastian Opitz